Xifos

Ifosfamide is indicated for the treatment of:

• Soft tissue sarcomas: Advanced or metastatic disease.
• Testicular cancer: Particularly refractory or relapsed cases, often in combination chemotherapy.
• Lymphomas: Hodgkin’s and non-Hodgkin’s lymphoma, as part of combination regimens.
• Other malignancies: Such as lung cancer, bladder cancer, osteosarcoma, and cervical cancer, depending on clinical protocols.

Off-label uses:

• Conditioning regimen prior to hematopoietic stem cell transplantation.
• Other cancers as determined by oncologists.

Adults:

• Typical dose: 1.2 to 2.5 g/m²/day intravenously over 30–120 minutes for 3 to 5 consecutive days per cycle.
• Total cycle dose usually ranges from 6 to 9 g/m².
• Cycles repeat every 3 to 4 weeks depending on response and toxicity.

Pediatrics:

• Dose calculated by body surface area; similar schedule to adults with adjustments based on tolerance.

Elderly:

• Cautious dosing recommended due to increased risk of toxicity. Dose reductions may be necessary.

Renal impairment:

• Dose adjustment advised in moderate to severe renal dysfunction.

Hepatic impairment:

• Use with caution; dose modification recommended in significant hepatic dysfunction.

Administration:

• Administer via intravenous infusion over 30 to 120 minutes.
• Ensure adequate hydration and uroprotection with mesna to prevent hemorrhagic cystitis.

Ifosfamide is an alkylating agent of the nitrogen mustard type. It is a prodrug that undergoes hepatic activation by cytochrome P450 enzymes to active metabolites including isophosphoramide mustard. These metabolites alkylate DNA by forming cross-links, primarily at the N7 position of guanine bases, which inhibits DNA replication and transcription, resulting in cell death. This cytotoxic effect primarily targets rapidly dividing cancer cells.

• Absorption: Administered intravenously, resulting in 100% bioavailability.
• Distribution: Widely distributed in body tissues; volume of distribution approximately 0.6 L/kg. Crosses the blood-brain barrier to some extent.
• Metabolism: Metabolized primarily in the liver by CYP3A4 and CYP2B6 enzymes to active and inactive metabolites including isophosphoramide mustard and acrolein.
• Half-life: Terminal half-life ranges from 7 to 15 hours.
• Excretion: Mainly renal excretion of metabolites; approximately 10–20% is excreted unchanged in the urine.

• Pregnancy: FDA Category D. Teratogenic and embryotoxic; contraindicated in pregnancy. Women of childbearing potential must use effective contraception during and for several months after treatment.
• Lactation: Unknown if excreted in human milk; breastfeeding is contraindicated during therapy and for an appropriate period afterward.

• Primary class: Antineoplastic agent
• Subclass: Alkylating agent, nitrogen mustard derivative

• Hypersensitivity to ifosfamide or excipients.
• Severe bone marrow suppression unrelated to malignancy.
• Severe hepatic or renal dysfunction (unless benefits outweigh risks).
• Pregnancy and breastfeeding.

• Hemorrhagic cystitis: Risk due to acrolein metabolite; prevent with adequate hydration and mesna co-administration.
• Myelosuppression: Severe neutropenia, thrombocytopenia, and anemia; regular blood counts required.
• Neurotoxicity: Encephalopathy can occur, ranging from mild confusion to coma; risk factors include high doses and renal impairment.
• Renal toxicity: Monitor renal function carefully.
• Pulmonary toxicity: Rare but possible; monitor for respiratory symptoms.
• Secondary malignancies: Risk of therapy-related leukemia or myelodysplastic syndrome.

Common:

• Nausea and vomiting
• Myelosuppression (neutropenia, thrombocytopenia, anemia)
• Fatigue
• Alopecia
• Hemorrhagic cystitis

Serious and rare:

• Neurotoxicity (encephalopathy, seizures, coma)
• Renal impairment
• Severe infections due to immunosuppression
• Pulmonary toxicity
• Secondary malignancies

• CYP3A4 inhibitors/inducers: May alter metabolism and toxicity profile.
• Other myelosuppressive agents: Increased bone marrow suppression risk.
• Nephrotoxic drugs: Increased risk of renal toxicity.
• Alcohol: May exacerbate central nervous system toxicity.
• Mesna: Required concomitantly to prevent urothelial toxicity.

• Emphasis on mesna use and hydration to prevent hemorrhagic cystitis is standard in treatment protocols.
• Increased awareness and monitoring recommendations for neurotoxicity have been included in recent guidelines.
• Dose modifications for patients with renal or hepatic impairment are now routinely recommended.
• Supportive care and infection prophylaxis remain critical during treatment.

• Store at 20°C to 25°C (68°F to 77°F); short excursions between 15°C and 30°C (59°F to 86°F) allowed.
• Protect from light and moisture; store in original packaging.
• Use reconstituted solutions promptly, discard unused portions according to protocol.
• Keep out of reach of children.